Search PubMed⌕ Search

Biomedical subjects

S Fletcher

Publications and source records attributed to S Fletcher.

At least 91 records · Page 5Linked to original sources
PubMed1994

Long-term outcome after intravenous magnesium sulphate in suspected acute myocardial infarction: the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2)

The second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) examined the effect of an intravenous regimen of magnesium sulphate in 2316 patients with suspected acute myocardial infarction. Treatment, according to a double-blind randomised protocol, was started with a loading injection, before any thrombolytic therapy, and continued with a maintenance infusion for a further 24 h. Cause-specific mortality of randomised patients has now been examined over 1.0-5.5 (mean 2.7) years of follow-up. Mortality rate from ischaemic heart disease was reduced by 21% (95% CI 5-35%, p = 0.01) and all-cause mortality rate reduced by 16% (2-29%, p = 0.03) in magnesium-treated patients. Magnesium protects the contractile function of the myocardium from reperfusion injury ("stunning") in experimental models; this observation accords with the 25% (7-39%, p = 0.009) reduction in early left ventricular failure in the magnesium group of LIMIT-2. For such protection to occur, magnesium must be raised by the time of reperfusion since the injury is immediate. In the clinical context the timing of magnesium treatment in relation to thrombolytic therapy or spontaneous reperfusion is likely to be critical. The early benefits of this simple and safe intervention are reflected in improved long-term survival.

Double-Blind Method↗
PubMed1994

Photomutagenicity assays in bacteria: factors affecting assay design and assessment of photomutagenic potential of para-aminobenzoic acid.

Photomutagenicity assays are required for regulatory submissions of some chemicals. As yet there are no well-validated protocols available for these assays. Critical factors which may contribute to the ability of a bacterial assay to detect photomutagens (e.g. dose of UV and test chemical, exposure conditions, light source, bacterial strains) were investigated using two known photomutagens, chlorpromazine and 8-methoxypsoralen. Salmonella typhimurium strains TA98, TA102 and TA1537 and Escherichia coli strains WP2 and WP2(pKM101) were used and differences in the responsiveness of these strains were observed with these substances. Both chemicals were detected using either UV exposure in suspension or on the agar plates. On the basis of these observations and on other results reported in the literature, recommendations are made on protocol aspects for assessing photomutagenic potential in routine screening tests. Using these recommendations the sunscreen para-aminobenzoic acid was tested in S.typhimurium strains TA98, TA100, TA1535, TA1537 and E. coli strains WP2 and WP2 (pKM101), using both plate irradiation and suspension exposure conditions. No evidence of mutagenic potential was detected.

4-Aminobenzoic Acid↗
PubMed1994

Investigation of the effects of intravenous magnesium sulphate on cardiac rhythm in acute myocardial infarction.

OBJECTIVE: To examine the effect of doubling serum magnesium concentration on the incidence of arrhythmias in patients with suspected acute myocardial infarction. DESIGN: Randomised double blind clinical trial. SETTING: Coronary care unit of a teaching hospital. PATIENTS: Clinical data were collected on 2316 randomised patients with suspected acute myocardial infarction. Holter monitoring was performed in a subgroup of 70 patients and analysed in 48 patients in whom acute myocardial infarction was confirmed. INTERVENTIONS: By random allocation, patients received either an intravenous loading dose of 8 mmol magnesium sulphate over five minutes plus 65 mmol over the next 24 hours, or equal volumes of saline. MAIN OUTCOME MEASURES: (a) Clinically documented arrhythmias; (b) use of antiarrhythmic treatments, cardioversion, and insertion of a pacemaker; (c) incidence of all abnormal rhythms during Holter monitoring. RESULTS: In the main trial the incidence of rhythm disturbance while in the coronary care unit (expressed as the odds ratio (OR) for magnesium: placebo and its 95% confidence interval) was not significantly different between treatment groups for ventricular fibrillation (OR 0.74; 0.46 to 1.20), ventricular tachycardia (OR 0.87; 0.63 to 1.20), supraventricular tachycardia (OR 0.69; 0.38 to 1.26), atrial fibrillation (OR 0.92; 0.69 to 1.23), or heart block of any degree (OR 1.17; 0.83 to 1.65). Sinus bradycardia was significantly more common in the magnesium group (OR 1.38; 1.03 to 1.85; p = 0.02). These findings were corroborated by the use of treatments for rhythm disturbance and the data from Holter monitoring. CONCLUSION: The regimen of intravenous magnesium sulphate used here had no significant effect on arrhythmia in acute myocardial infarction. The reduction in mortality that has been shown with this form of treatment is not attributable to suppression of life threatening rhythm disturbances.

Aged↗
PubMed1994

Nocturnal intermittent peritoneal dialysis.

Automated methods of peritoneal dialysis have developed as alternative methods of treatment to CAPD. We review our experience of 47 patients treated with nocturnal intermittent peritoneal dialysis (NIPD). Patients receive a nocturnal exchange of 15-25 litres of dialysate with the peritoneum left dry during the day. If biochemical control is inadequate, 1 litre of dialysate is left in during the day. Indications for NIPD included social reasons and CAPD failure due to poor ultrafiltration or problems related to raised intra-abdominal pressure. Some features of biochemical control were less good with NIPD compared with CAPD with higher phosphate (2.18 mmol/l versus 1.83 mmol/l, P < 0.001); creatinine (1256 mumol/l versus 1085 mumol/l, P < 0.001); and potassium (4.92 mmol/l versus 4.64 mmol/l, P = 0.056) in patients changing between CAPD and NIPD. Overall peritonitis rate on NIPD was one episode per 47.1 months compared with a rate of one episode per 17.5 months for patients commencing CAPD over the same period. Conversion from CAPD to NIPD was successful in all six cases for problems related to raised intra-abdominal pressure on CAPD and in six of nine patients transferred due to poor ultrafiltration. NIPD is a useful form of treatment and we believe that the increased cost is offset by the reduced peritonitis rate.

Adult↗
PubMed1993

Chirality in the umbilical cord.

OBJECT: To determine the chiral varieties of the vascular helix of the umbilical cord and find their normal proportions. DESIGN: Differences between the sexes were tested by a chi 2 test and the hypothesis that left-handed types occur in 50% of cases was tested using the binomial distribution. SETTING: United Arab Emirates. SUBJECT: Gulf Arab singletons from consecutive normal births, 100 male and 100 female. RESULTS: Left-handed helices predominate at 76.5%; right-handed contribute 15.5%; mixed forms, where both chiralities co-exist, were found in 6.5%; indeterminable chirality due to poor helix formation, or varices, reached 1.5%. A significant sex difference could not be established. Chiral generation, on genetic and mechanical-rotational hypotheses, is discussed. CONCLUSION: The chirality of the cord is easily determined and is the sole distinguishing feature of the cord. Chirality should be entered in the birth record and in pathological descriptions for whatever value it may have in relation to fetal, or postnatal, characteristics and morbidity.

Female↗
PubMed1992

Intravenous magnesium sulphate in suspected acute myocardial infarction: results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2)

The cardiovascular actions of the magnesium ion at pharmacological concentrations include coronary and systemic vasodilatation, platelet inhibition, and antiarrhythmic effects. Magnesium has also been reported to protect myocardial tissue in experimental models of ischaemia and reperfusion. Several small clinical trials in suspected acute myocardial infarction have suggested that early mortality can be reduced by intravenous infusion of magnesium salts in the acute phase, but none has been of sufficient size to be conclusive. We therefore conducted a randomised, double blind, placebo controlled study in 2316 patients with suspected acute myocardial infarction who received either intravenous magnesium sulphate (8 mmol over 5 min followed by 65 mmol over 24 h) or physiological saline. The primary outcome measure was 28-day mortality, which was ascertained in 99.3% of patients. The groups were well balanced for prognostic factors. By intention-to-treat analysis mortality from all causes was 7.8% in the magnesium group and 10.3% in the placebo group (2p = 0.04), a relative reduction of 24% (95% confidence interval 1-43%). Within the coronary care unit the incidence of left ventricular failure was reduced by 25% (7-39%) in the magnesium group (2p = 0.009). There was no significant difference between the groups in the incidence of heart block or the use of antiarrhythmic drugs, direct-current cardioversion, or temporary pacing. Myocardial infarction was confirmed in 65% of each group, with closely similar rises in cardiac enzymes. The side-effects of magnesium treatment were transient flushing, related to speed of injection of the loading dose, and an increased incidence of sinus bradycardia (2p = 0.02). Exploratory subgroup analyses of 28-day mortality did not indicate any effect modification by thrombolysis or aspirin, or by previous treatment with beta blockers, calcium antagonists, or diuretics. Intravenous magnesium sulphate is a simple, safe, and widely applicable treatment. Its efficacy in reducing early mortality of myocardial infarction is comparable to, but independent of, that of thrombolytic or antiplatelet therapy.

Aged↗
PubMed1992

Differential cardiovascular effects of propranolol, atenolol, and pindolol measured by impedance cardiography.

We have evaluated Sramek's method of impedance cardiography as a non-invasive way of detecting the cardiovascular effects of drugs. We made cardiovascular measurements using the method during passive tilting and exercise 2 h after the oral administration of atenolol (50 and 100 mg), propranolol (40 and 80 mg), pindolol (5 and 10 mg), and placebo in seven separate studies involving eight healthy male volunteers. Equivalent doses of the pure antagonists atenolol (beta 1) and propranolol (beta 1, beta 2) produced similar reductions in heart rate, systolic blood pressure, and cardiac index, and increases in stroke volume and total peripheral resistance, particularly during exercise. In contrast the partial agonist pindolol produced increases in heart rate and cardiac index, and reductions in peripheral resistance at rest. During passive tilting and exercise pindolol reduced heart rate, but cardiac output and total peripheral resistance were unchanged except at the highest levels of exercise. The similar cardiovascular effects of atenolol and propranolol, but differing effects of pindolol, are consistent with reports using other methods of measurement. This suggests that impedance cardiography may have a place in the non-invasive assessment of the cardiovascular effects of drugs.

Adult↗
PubMed1992

Plasma total and free concentrations of bupivacaine and lignocaine in mother and fetus following epidural administration, singly or together.

Forty six women undergoing elective caesarean section under epidural blockade were given 20 ml of either bupivacaine 0.5% plain (B) or with adrenaline 5 microg/ml (B + A), lignocaine 2% with adrenaline 5 microg/ml (L + A) or a mixture of equal parts of L + A and B + A (BLA). Further doses of the same solution were given at 20 min if necessary. Free and total plasma concentrations of the local anaesthetics were measured in maternal venous plasma 10, 20, 40, 60 and 120 min after the main dose and in umbilical venous plasma at delivery. Protein binding of both drugs was significantly higher in mother than baby. Lignocaine did not affect bupivacaine binding but lignocaine binding was higher in group BLA than L + A. Otherwise the presence of one drug had little effect on the disposition of the other drug in mother or baby. No plasma concentrations were considered toxic. Adrenaline did not reduce maternal C(max) of free bupivacaine and appeared to be associated with increased fetal uptake of bupivacaine.

Journal Article↗
PubMed1992

Modification of the circadian rhythm of onset of acute myocardial infarction by long-term antianginal treatment.

OBJECTIVE: To elucidate the mechanism of the circadian pattern of onset of acute myocardial infarction by examining the effects of prior antianginal treatment upon it. DESIGN: Retrospective analysis of clock time of the onset of acute myocardial infarction by linear modelling to define the circadian distribution of hourly onset rates and to examine the deviation of treated groups of patients from this distribution. SETTING: Coronary care unit in a general hospital taking unselected acute admissions from a district of 0.9 million people. PATIENTS: A series of 2231 patients with confirmed acute myocardial infarction. RESULTS: A major 24 h cycle and smaller 12 h and 6 h cycles were present in patients not taking antianginal medication. Onset rates varied twofold over the day, with maxima around 10.00 am and 10.00 pm. This pattern was unchanged in patients on prior treatment with regular nitrates, but in those who had been taking a beta blocker or a calcium antagonist the 24 h cycle was absent. CONCLUSIONS: These results are best explained by the shared property of beta blockers and calcium antagonists to reduce blood pressure and myocardial oxygen demand. The mid-morning peak of the onset of myocardial infarction is attributable to the physiological increase in sympathetic drive and cardiac work at that time. The data are not consistent with the triggering of the 24 h periodicity by fluctuations in coronary tone or haemostatic activity.

Adrenergic beta-Antagonists↗
PubMed1992

Bilateral retinopathy, aplastic anaemia, and central nervous system abnormalities: a new syndrome?

A male infant was found to have bilateral exudative retinopathy at 6 months of age. A month later severe aplastic anaemia was diagnosed, eventually leading to the infant's death. Additional features of this seemingly new syndrome were intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia because of cerebellar hypoplasia, cerebral calcifications, extensor hypertonia, and progressive psychomotor retardation.

Anemia, Aplastic↗
PubMed1992

Half a loaf is better than waiting for the bread truck. A computerized mini-medical record for outpatient care.

We describe a locally developed system for partial computer storage of medical data, called the mini-medical record system. The system produces a typed face sheet prior to each patient visit. The face sheet, which also serves as a progress note, contains patient demographic data, medical problem lists, previous vital signs, allergies, medication profile, and health maintenance reminders. Between regularly scheduled visits, all computerized data are available by computer printout for unscheduled visits to walk-in clinics and the emergency department. Structured reports are generated by the system that describes each resident and faculty members' practice. Quality assurance reports are also available. Since the system draws from several already existing databases, new data entry requirements are modest and cost to the institution is low. Partially computerized systems can be developed inexpensively and are well received in multispecialty practices, where interphysician communication is vital.

Ambulatory Care Information Systems↗
PubMed1992

Innovative treatment or ethical headache? Fetal transplantation in Parkinson's disease.

Current drug therapies have limitations in controlling Parkinson's disease in the long term. Early results of fetal cell transplantation are encouraging, suggesting it may help many sufferers. The technique raises ethical considerations, particularly with regard to collection of fetal tissue. Nurses must form their own opinions on the technique, and while they may opt out of the actual operations involved, they still have a duty of care to these patients.

Aborted Fetus↗